Methamphetamine Delivers ‘One-Two’ Punch to the Brain

Mechanism may knock out brain’s ability to “just say no.”

UPTON, NY — A new brain-imaging study at the U.S. Department of
Energy’s Brookhaven National Laboratory reveals that, compared with
people who don’t use drugs, people who abuse methamphetamine have
fewer receptors for dopamine, a brain chemical associated with
feelings of reward and pleasure. Furthermore, in the drug abusers, low
dopamine receptor levels were linked with reduced metabolic activity
in a brain region that regulates motivation and “drive.”

“These findings mirror those from a similar
Brookhaven study on cocaine abusers, and
may help explain why drugs addicts lose control and take drugs
compulsively,” said
Nora Volkow, the lead researcher. The new results
appear in the December issue of the American Journal of Psychiatry.

Abuse
of methamphetamine — also known as “speed” or “crank” — has risen
dramatically over the past decade in several areas of the United
States and around the world. “It has become a significant public
health problem,” said Volkow, whose team has worked for years to
uncover the neurological mechanisms of addiction.

Previous imaging studies at Brookhaven and elsewhere have shown
that a common abnormality in drug-addicted subjects — including
alcoholics, cocaine abusers, and heroin abusers — is a
lower-than-normal level of so-called dopamine D2 receptors. The
Brookhaven scientists have also shown that, in cocaine abusers,
dopamine D2 receptor levels are linked with lower metabolic activity
in the orbitofrontal cortex of the brain.

“Disruption of the orbitofrontal cortex is associated with
obsessive and compulsive behaviors,” Volkow said. “So we hypothesized
that disruption of this brain region, resulting from depletion of
dopamine receptors, could lead to compulsive cocaine intake.”

To find out if the same mechanism might be at work in
methamphetamine abusers, the scientists measured dopamine D2 receptor
levels and orbitofrontal cortex activity in 15 methamphetamine abusers
— who were not taking drugs at the time of the study — and 20
non-drug-abusing comparison subjects.

These brain scans show that dopamine receptor
levels are lower in methamphetamine abusers than in control
subjects. High dopamine receptor levels appear red, while low
levels appear yellow/green.

To measure D2 receptor levels, each study volunteer was given an
injection of a radiotracer, a radioactive chemical “tag” designed to
bind to the D2 receptors in the brain. The researchers then scanned
the subjects’ brains using a positron emission tomography (PET)
camera. The PET camera picks up the radioactive signal of the tracer
and shows where it is bound to receptors. The strength of the signal
indicates the concentration of receptors.

To measure metabolic activity in the orbitofrontal cortex, a
similar PET study was performed, this time using a radiotracer
designed to bind to glucose, the brain’s metabolic “fuel.” Higher
levels of glucose on PET scans indicate higher metabolic activity.

As hypothesized, the methamphetamine abusers had significantly
lower levels of D2 receptors than the control subjects. And the lower
the number of D2 receptors, the lower the metabolic activity in the
orbitofrontal cortex.

The blunted orbitofrontal cortex activity in these drug abusers
“reduces the ability of all other stimuli to trigger a reward
response,” said Volkow. “Ordinary stimuli are not strong enough to
activate the circuits.”

Administration of methamphetamine, however, releases such an
enormous amount of dopamine, that all available dopamine receptors are
activated, no matter how few there are. This very strong dopamine
signal then becomes the only stimulus capable of boosting activity in
the orbitofrontal cortex, Volkow said, making it very hard for the
addict to resist the drug.

This work was funded by the U.S. Department of Energy, which
supports basic research in a variety of scientific fields; the
National Institute on Drug Abuse, part of the National Institutes of
Health; and the Office of National Drug Control Policy.

The U.S. Department of Energy's Brookhaven National Laboratory conducts
research in the physical, biomedical, and environmental sciences, as well
as in energy technologies. Brookhaven also builds and operates major
facilities available to university, industrial, and government scientists.
The Laboratory is managed by Brookhaven Science Associates, a limited
liability company founded by Stony Brook University and Battelle, a
nonprofit applied science and technology organization.